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In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.

BackgroundThis study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND).MethodsWe evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative 68Ga- or 18F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA− or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6–12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR.ResultsForty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9–17.1 95% CI) and BCR (OR 8.1, 2.9–22.6 95% CI).ConclusionPreoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

Jacques Cinq-Mars was one of the cohort of archaeologists attending the University of Wisconsin Madison in the 1960s who were the vanguard of archaeological research in northern Canada and Alaska. Among Jacques' contemporaries were W.N. (Bill) Irving, Donald W. Clark, Richard Morlan, William B. Workman, Roger Powers, and Anne Shinkwin who, along with Jacques, established the baseline for our understanding of archaeology in the North American Arctic and Subarctic. In 1971 Jacques, along with Don Clark of the National Museum of Man, also undertook surveys in the Keele River and Fort Good Hope area and carried out small-scale excavations and surveys in the lake region to the west of the Mackenzie River, including the initial work at Yellow Lake and the identification of the nearby Tertiary Hills clinker source. Jacques' research for the Mackenzie Corridor project saw continued work at Yellow Lake and exploratory excavations at two sites on the Porcupine River: the caribou interception site at Rat Indian Creek and the house pit site at Old Chief Creek.

Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. Male Wistar rats (4 per group) were injected intravenously with 1 MBq of (111)In-labeled octreotide (OCT), minigastrin (MG), bombesin (BOM), or exendin (EX), together with a potential inhibitor of renal uptake (lysine [Lys], poly-glutamic acid [PGA], and Gelofusine [GF], a gelatin-based plasma expander) or phosphate-buffered saline as a control. Organ uptake at 20 h after injection was determined as the percentage of injected activity per gram (%IA/g). Lys, PGA, and GF were also combined to determine whether an additive effect could be obtained. The localization of the peptides in the kidneys was investigated by autoradiography using a phosphor imager. OCT accumulation in the kidney was inhibited by Lys and GF (40.7%-45.1%), whereas PGA was ineffective. On the other hand, renal uptake of BOM, MG, and EX was inhibited by PGA and GF (15.4%-85.4%), whereas Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting OCT uptake, whereas PGA and GF had additive effects for the inhibition of EX uptake. The amount of kidney uptake correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex, as indicated by autoradiography. Inhibition of renal accumulation of the radiopeptides tested could be achieved by either Lys or PGA but not by both at the same time, suggesting 2 different uptake mechanisms. The differences in renal accumulation of radiopeptides may be related to the number of charges of a molecule. GF is the only compound that inhibited renal accumulation of all radiopeptides tested. Additional experiments are needed to further elucidate these findings and to optimize inhibition of renal accumulation of radiopeptides to reduce the kidney dose in PRRT.

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BackgroundActivated synovial fibroblasts (SF) play an important role in the pathogenesis of rheumatoid arthritis (RA). They contribute to the pro-inflammatory environment in the joint as well as to the degradation of cartilage. Depleting SF could ameliorate both the symptoms of joint inflammation and degradation in RA. SF are characterised by the expression of Fibroblast Activation Protein (FAP). Here, we investigated the potential of photodynamic therapy (PDT) targeting FAP to selectively induce cell death in these cells as well as in synovial tissue from RA patients. In PDT, a light-sensitive molecule is delivered to a target cell and activated with light of a specific wavelength. This causes cell death through the production of reactive oxygen species.MethodsThe anti-FAP antibody 28 H1 was conjugated with the photosensitizer IRDye700DX (28 H1–700DX). In vitro PDT assays were performed with 3 T3 fibroblasts stably transfected with FAP. 3T3-FAP cells were incubated with 28 H1–700DX or a control conjugate for 4 hours, and exposed to varying 690 nm light exposures. Subsequently, cell viability was measured using the CellTiter-Glo assay. For ex vivo evaluation of PDT efficiency, human RA synovial tissue obtained after joint replacement surgery was processed into standardised 6 mm biopsies and used for FAP-based PDT. The biopsies were incubated with 28 H1–700DX for 4 hours, subjected to 52 J/cm2 light exposure and fixed in formalin after 1 hour. Tissue was then embedded in paraffin and stained for the presence of gH2AX and caspase 3 as indicators of DNA double-strand breaks and early apoptosis on sequential slides. The presence of FAP was also determined on subsequent slides.ResultsThe effect of PDT was optimal at 13.7 J/cm2 light exposure to 3T3-FAP cells incubated with 6.67 pM 28 H1–700DX, which dramatically reduced cell viability with 89.27%±2.48 compared to control (p<0.001). No cell death was observed with the control 700DX-conjugate (p=0.16).In the PDT experiment on human RA synovial biopsies, the groups incubated with 28 H1–700DX and exposed to light showed apparent cell death in the synovial tissue as evidenced by the positive staining of both the gH2AX and caspase 3 markers (figure J and K). Staining of these markers co-localised with areas of high FAP staining (figure L). This was not the case in the control samples that were not exposed to either 28 H1–700DX and/or light (figure A – I). All biopsies did show FAP staining indicating that the cell death was only achieved when the biopsies were exposed to both the antibody and the light.ConclusionsWe have demonstrated fibroblast-specific cell death by targeted PDT using 700DX-conjugated 28 H1. Furthermore, we demonstrated that PDT also induces cell death of FAP-positive cells in synovial tissue from RA patients, suggesting FAP-targeted PDT as a promising new tool in treating RA.Disclosure of InterestNone declared

A comprehensive look at the practice of nuclear medicine training and practice in Germany is presented. Overall there are about 1,000 registered specialists in nuclear medicine in Germany compared to nearly 7,000 radiologists.